Colocalization of Aldehyde Dehydrogenases and Fe/NADPH-Induced Lipid Peroxidation in Tissue Sections of Rat Retina

Pinazo-Durán,; Verdejo, C; Azorı́n, Inmaculada; Renau‐Piqueras, Jaime; Iborra, Francisco J.

doi:10.1159/000055591

Cited by 12 publications

(9 citation statements)

References 28 publications

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“…Previously, others have studied oxidative stress with respect to the effect of other toxic substances in the visual system (Veriac et al, 1993;Babizhayev and Costa, 1994;Harris et al, 2000;Pinazo-Duran et al, 2000). Many xenobiotics, such as environmental pollutants, pharmacological substances, and alcohol, induce free radical formation in the developing retina (Stromland and Pinazo-Duran, 2002); however, prior to this study, no information was available regarding whether early exposure to MA also causes lipid peroxidation to occur in the developing retina.…”

Section: Discussionmentioning

confidence: 99%

Methamphetamine and lipid peroxidation in the rat retina

Melo

Rodrigues

Pinazo-Durán

et al. 2005

Birth Defects Research

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Section: Discussionmentioning

confidence: 99%

Methamphetamine and lipid peroxidation in the rat retina

Melo

Rodrigues

Pinazo-Durán

et al. 2005

Birth Defects Research

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“…The results of this study suggest that a functional RDH12 is essential to photoreceptor physiology because of its role in the regulation of retinoic acid biosynthesis. Retinoic acid is produced in photoreceptors from retinaldehyde diffusing from illuminated rhodopsin into the inner segments of photoreceptors (32), where retinaldehyde is oxidized irreversibly to retinoic acid by cytosolic aldehyde dehydrogenases (33). The amount of all-trans-retinaldehyde generated in the eye is variable, because it depends on ambient light intensity, and can theoretically reach concentrations as high as 3 mM (13).…”

Section: Discussionmentioning

confidence: 99%

Overproduction of Bioactive Retinoic Acid in Cells Expressing Disease-associated Mutants of Retinol Dehydrogenase 12

Lee

Belyaeva

Popov

et al. 2007

Journal of Biological Chemistry

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Retinol dehydrogenase 12 (RDH12) is an NADP؉ -dependent oxidoreductase that in vitro catalyzes the reduction of all-transretinaldehyde to all-trans-retinol or the oxidation of retinol to retinaldehyde depending on substrate and cofactor availability. Recent studies have linked the mutations in RDH12 to severe early-onset autosomal recessive retinal dystrophy. The biochemical basis of photoreceptor cell death caused by mutations in RDH12 is not clear because the physiological role of RDH12 is not yet fully understood. Here we demonstrate that, although bi-directional in vitro, in living cells, RDH12 acts exclusively as a retinaldehyde reductase, shifting the retinoid homeostasis toward the increased levels of retinol and decreased levels of bioactive retinoic acid. The retinaldehyde reductase activity of RDH12 protects the cells from retinaldehyde-induced cell death, especially at high retinaldehyde concentrations, and this protective effect correlates with the lower levels of retinoic acid in RDH12-expressing cells. Disease-associated mutants of RDH12, T49M and I51N, exhibit significant residual activity in vitro, but are unable to control retinoic acid levels in the cells because of their dramatically reduced affinity for NADPH and much lower protein expression levels. These results suggest that RDH12 acts as a regulator of retinoic acid biosynthesis and protects photoreceptors against overproduction of retinoic acid from all-trans-retinaldehyde, which diffuses into the inner segments of photoreceptors from illuminated rhodopsin. These results provide a novel insight into the mechanism of retinal degeneration associated with mutations in RDH12 and are consistent with the observation that RDH12-null mice are highly susceptible to light-induced retinal apoptosis in cone and rod photoreceptors.Vitamin A derivatives serve two different physiological functions: detection of light in vision and regulation of gene transcription during differentiation and development of cells and tissues. The first function is carried out by 11-cis-retinaldehyde, which serves as a visual chromophore (1). Upon absorption of light, 11-cis-retinaldehyde covalently bound to rod and cone opsins is isomerized to all-trans-retinaldehyde (1). All-transretinaldehyde dissociates from the opsin and is reduced in photoreceptors to all-trans-retinol, which is translocated to retinal pigment epithelium (RPE) and esterified to all-trans-retinyl esters. The resulting retinyl esters are isomerized and hydrolyzed to produce 11-cis-retinol. 11-cis-retinol is oxidized in RPE to 11-cis-retinaldehyde, which is then returned to photoreceptor cells. This sequence of events is known as the retinoid visual cycle and allows for regeneration of 11-cis-retinaldehyde for the next round of visual signal transduction.The function of vitamin A in gene transcription is mediated by retinoic acid, the activating ligand of nuclear transcription factors, retinoic acid receptors (2). Retinoic acid is required for differentiation and development of many tissues and is also o...

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“…ALDHs are a group of NADP-dependent enzymes that catalyze the conversion of aldehydes into acid metabolites. They also participate in the metabolism of alcohols [2], biogenic amines [3], vitamins [4], steroids [5] and lipids [6,7], as well as in the biotransformation of numerous drugs and environmental agents [8]. …”

Section: Introductionmentioning

confidence: 99%

Retinoic acid modulates retinaldehyde dehydrogenase 1 gene expression through the induction of GADD153–C/EBPβ interaction

Elizondo

Medina-Díaz

Cruz

et al. 2009

Biochemical Pharmacology

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Mammalian class I aldehyde dehydrogenase (ALDH) plays an important role in the biosynthesis of the hormone retinoic acid (RA), which modulates gene expression and cell differentiation. RA has been shown to mediate control of human ALDH1 gene expression through modulation of the retinoic acid receptor α (RARα) and the CCAAT/enhancer binding protein β (C/EBPβ). The positive activation of these transcription factors on the ALDH1 promoter is inhibited by RA through a decrease of C/EBPβ binding to the ALDH1 CCAAT box response element. However, the mechanism of this effect remains unknown. Here we report that the RARα/retinoid X receptor β (RXRβ) complex binds to the mouse retinaldehyde dehydrogenase 1 (Raldh1) promoter at a non-consensus RA response element (RARE) with similar affinity to that of the consensus RARE. We found that C/EBPβ binds to a Raldh1 CCAAT box located at -82/-58 bp, adjacent to the RARE. Treatment with RA increases GADD153 and GADD153-C/EBPβ interaction resulting in a decreased cellular availability of C/ EBPβ for binding to the Raldh1 CCAAT box. These data support a model in which high RA levels inhibit Raldh1 gene expression by sequestering C/EBPβ through its interaction to GADD153.

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Colocalization of Aldehyde Dehydrogenases and Fe/NADPH-Induced Lipid Peroxidation in Tissue Sections of Rat Retina

Cited by 12 publications

References 28 publications

Methamphetamine and lipid peroxidation in the rat retina

Methamphetamine and lipid peroxidation in the rat retina

Overproduction of Bioactive Retinoic Acid in Cells Expressing Disease-associated Mutants of Retinol Dehydrogenase 12

Retinoic acid modulates retinaldehyde dehydrogenase 1 gene expression through the induction of GADD153–C/EBPβ interaction

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